Is E2F4 p.Val209Glu (c.626T>A) pathogenic?

E2F4 p.Val209Glu (c.626T>A) is classified Uncertain significance in E2F4 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-01-19). AlphaMissense: likely pathogenic (0.9919); Absent from gnomAD v4.1.

How common is E2F4 p.Val209Glu (c.626T>A) in the general population?

E2F4 p.Val209Glu (c.626T>A) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about E2F4 p.Val209Glu (c.626T>A)?

AlphaMissense predicts likely pathogenic (score 0.9919) — an in-silico prediction, not a clinical call.

E2F4 p.Val209Glu

c.626T>A · rs2507187508 · VCV2272292

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9919 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

2/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.9919	likely pathogenic
REVEL	0.666	pathogenic-leaning
SaProt	LLR -7.11	tolerated
⇒ AlphaMissense and REVEL call this damaging; SaProt does not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.9	GERP 2.1, phastCons 1
Regional constraint	o/e 0.99	unconstrained · MANE · 3,701 bp · p 0.93 · regional, not allelic
Overall
CADD	29.6	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: E2F4
Protein: p.Val209Glu
Coding: c.626T>A
MANE Select: NM_001950
dbSNP: rs2507187508
Type: single nucleotide variant
Location: chr16:67194798 (GRCh38)
Gene constraint: LOEUF 0.615 · pLI 0.36 (gnomAD)
Structure: AlphaFold pLDDT 65.56 · 2 PDB

Full E2F4 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

E2F4 p.Ala138Val Uncertain significance ★ ⚠ same type
E2F4 p.Ala150Thr Uncertain significance ★ ⚠ same type
E2F4 p.Ala239Gly Uncertain significance ★ ⚠ same type
E2F4 p.Ala239Pro Uncertain significance ★ ⚠ same type
E2F4 p.Ala2Gly Uncertain significance ★ ⚠ same type
E2F4 p.Ala340Ser Uncertain significance ★ ⚠ same type
E2F4 p.Ala4Pro Uncertain significance ★ ⚠ same type
E2F4 p.Arg126Gln Uncertain significance ★ ⚠ same type

Built on 18 open, versioned datasets — ClinVar, gnomAD, AlphaMissense, REVEL, ClinGen & more — plus Sugi Variant's own cross-source analysis. Source data 2026-01–2026-10, ClinVar 2026-10. Full sources & versions →

Cite Sugi Variant

Gür T. Sugi Variant: A Deterministic Per-Variant Germline Reference from a Knowledge Graph for Humans and AI Agents. 2026. doi:10.5281/zenodo.21509445. This variant: https://sugi.bio/variant/e2f4-p-val209glu (accessed [today's date]).

Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown